Summary: A novel protein (HBHA)has been identified on the surface of mycobacteria including M. tuberculosis, the causative agent of TB, which appears to promote the interaction of mycobacteria with host cells. Methods have been developed at CBER for the purification of this unique protein. Evidence suggests that this protein undergoes a post-translational modification that effects both function and immunogenicity. Important binding sites and immunological epitopes have been identified and characterized. Specific regions that interculate into the bacterial membrane, that form coiled-coil initiated interactions, and that bind to proteoglycans have been identified. The role of this protein in attachment of mycobacteria to host tissues and in other bacterial interactions continues to be investigated in detail using Mabs developed at CBER against HBHA. Importantly, HBHA appears to be crucial for promoting the dissemination of Mtb from the lung to other tissues, a process that is blocked by anti-HBHA antibodies. New evidence indidates that HBHA subunit vaccines are very effective at protecting against tuberculosis is the mouse model of TB. The current focus is on developing efficient methods for the purification of immunologically potent antigen for use as a TB vaccine and on characterizing the nature of the protective immune response to the subunit HBHA vaccine.